scholarly journals Dietary Phytochemicals Targeting Cancer Stem Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 899 ◽  
Author(s):  
Alena Liskova ◽  
Peter Kubatka ◽  
Marek Samec ◽  
Pavol Zubor ◽  
Milos Mlyncek ◽  
...  

There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, invasiveness, metastasis formation, and therapy resistance. Anticancer effects of phytochemicals are also directed to target CSCs. Here we provide a comprehensive review of dietary phytochemicals targeting CSCs. Moreover, we evaluate and summarize studies dealing with effects of dietary phytochemicals on CSCs of various malignancies in preclinical and clinical research. Dietary phytochemicals have a significant impact on CSCs which may be applied in cancer prevention and treatment. However, anticancer effects of plant derived compounds have not yet been fully investigated in clinical research.

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Saurabh Pratap Singh ◽  
Richa Singh ◽  
Om Prakash Gupta ◽  
Shalini Gupta ◽  
Madan Lal Brahma Bhatt

Mounting evidence from the literature suggests the existence of a subpopulation of cancer stem cells (CSCs) in almost all types of human cancers. These CSCs possessing a self-renewal capacity inhabit primary tumors and are more defiant to standard antimitotic and molecularly targeted therapies which are used for eliminating actively proliferating and differentiated cancer cells. Clinical relevance of CSCs emerges from the fact that they are the root cause of therapy resistance, relapse, and metastasis. Earlier, surgery, chemotherapy, and radiotherapy were established as cancer treatment modalities, but recently, immunotherapy is also gaining importance in the management of various cancer patients, mostly those of the advanced stage. This review abridges potential off-target effects of inhibiting CSC self-renewal pathways on immune cells and some recent immunological studies specifically targeting CSCs on the basis of their antigen expression profile, even though molecular markers or antigens that have been described till date as expressed by cancer stem cells are not specifically expressed by these cells which is a major limitation to target CSCs. We propose that owing to CSC stemness property to mediate immunotherapy response, we can apply a combination therapy approach by targeting CSCs and tumor microenvironment (TME) along with conventional treatment strategies as an effective means to eradicate cancer cells.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1062
Author(s):  
Adriana G. Quiroz-Reyes ◽  
Paulina Delgado-Gonzalez ◽  
Jose Francisco Islas ◽  
Juan Luis Delgado Gallegos ◽  
Javier Humberto Martínez Martínez Garza ◽  
...  

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. TRAIL has been widely studied as a novel strategy for tumor elimination, as cancer cells overexpress TRAIL death receptors, inducing apoptosis and inhibiting blood vessel formation. However, cancer stem cells (CSCs), which are the main culprits responsible for therapy resistance and cancer remission, can easily develop evasion mechanisms for TRAIL apoptosis. By further modifying their properties, they take advantage of this molecule to improve survival and angiogenesis. The molecular mechanisms that CSCs use for TRAIL resistance and angiogenesis development are not well elucidated. Recent research has shown that proteins and transcription factors from the cell cycle, survival, and invasion pathways are involved. This review summarizes the main mechanism of cell adaption by TRAIL to promote response angiogenic or pro-angiogenic intermediates that facilitate TRAIL resistance regulation and cancer progression by CSCs and novel strategies to induce apoptosis.


Author(s):  
Sarthak Sahoo ◽  
Atchuta Srinivas Duddu ◽  
Adrian Biddle ◽  
Mohit Kumar Jolly

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 965 ◽  
Author(s):  
Park ◽  
Choi ◽  
Nam

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that lacks targeted therapy options, and patients diagnosed with TNBC have poorer outcomes than patients with other breast cancer subtypes. Emerging evidence suggests that breast cancer stem cells (BCSCs), which have tumor-initiating potential and possess self-renewal capacity, may be responsible for this poor outcome by promoting therapy resistance, metastasis, and recurrence. TNBC cells have been consistently reported to display cancer stem cell (CSC) signatures at functional, molecular, and transcriptional levels. In recent decades, CSC-targeting strategies have shown therapeutic effects on TNBC in multiple preclinical studies, and some of these strategies are currently being evaluated in clinical trials. Therefore, understanding CSC biology in TNBC has the potential to guide the discovery of novel therapeutic agents in the future. In this review, we focus on the self-renewal signaling pathways (SRSPs) that are aberrantly activated in TNBC cells and discuss the specific signaling components that are involved in the tumor-initiating potential of TNBC cells. Additionally, we describe the molecular mechanisms shared by both TNBC cells and CSCs, including metabolic plasticity, which enables TNBC cells to switch between metabolic pathways according to substrate availability to meet the energetic and biosynthetic demands for rapid growth and survival under harsh conditions. We highlight CSCs as potential key regulators driving the aggressiveness of TNBC. Thus, the manipulation of CSCs in TNBC can be a targeted therapeutic strategy for TNBC in the future.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1136 ◽  
Author(s):  
Eva Rodriguez-Aznar ◽  
Lisa Wiesmüller ◽  
Bruno Sainz ◽  
Patrick C. Hermann

Metastasis and tumor progression are the major cause of death in patients suffering from pancreatic ductal adenocarcinoma. Tumor growth and especially dissemination are typically associated with activation of an epithelial-to-mesenchymal transition (EMT) program. This phenotypic transition from an epithelial to a mesenchymal state promotes migration and survival both during development and in cancer progression. When re-activated in pathological contexts such as cancer, this type of developmental process confers additional stemness properties to specific subsets of cells. Cancer stem cells (CSCs) are a subpopulation of cancer cells with stem-like features that are responsible for the propagation of the tumor as well as therapy resistance and cancer relapse, but also for circulating tumor cell release and metastasis. In support of this concept, EMT transcription factors generate cells with stem cell properties and mediate chemoresistance. However, their role in pancreatic ductal adenocarcinoma metastasis remains controversial. As such, a better characterization of CSC populations will be crucial in future development of therapies targeting these cells. In this review, we will discuss the latest updates on the mechanisms common to pancreas development and CSC-mediated tumor progression.


2020 ◽  
pp. 232020682096086
Author(s):  
Ambika Murugesan ◽  
B. Sekar ◽  
R. Saranyan ◽  
E. Manivannan ◽  
M. Rajmohan

Aim: Cancer stem cells (CSCs) or tumor-initiating cells have self-renewal and uncontrolled tumor growth capacity that promotes metastasis and recurrence. Challenges in anticancer have found a lateral dimension of treatment against a new pattern of tumor microcirculation, known as vasculogenic mimicry (VM), involved in cancer progression. Increasing evidence suggest that CSCs are involved in the formation of VM. In this review the correlation between CSCs and VM formation is been enlightened. Materials and Methods: The literature search was done in Medline, PubMed, Wiley, Science Direct, and Scopus. The keywords used for database search were cancer stem cells, vasculogenic mimicry, and anticancer therapy. Results: A total of 112 articles appeared from various sources, of which 102 were subjected for screening and 20 were related to the research objective. Conclusion: Based on the literature a positive correlation exists between CSC and VM, which plays a key role in tumor progression, and hence, can serve as a potential target in anticancer therapy.


Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 441
Author(s):  
Na Kyeong Lee ◽  
Vinoth Kumar Kothandan ◽  
Sangeetha Kothandan ◽  
Youngro Byun ◽  
Seung Rim Hwang

Cancer stem cells (CSCs), which have the capacity to self-renew and differentiate into various types of cells, are notorious for their roles in tumor initiation, metastasis, and therapy resistance. Thus, underlying mechanisms for their survival provide key insights into developing effective therapeutic strategies. A more recent focus has been on exosomes that play a role in transmitting information between CSCs and non-CSCs, resulting in activating CSCs for cancer progression and modulating their surrounding microenvironment. The field of CSC-derived exosomes (CSCEXs) for different types of cancer is still under exploration. A deeper understanding and further investigation into CSCEXs’ roles in tumorigenicity and the identification of novel exosomal components are necessary for engineering exosomes for the treatment of cancer. Here, we review the features of CSCEXs, including surface markers, cargo, and biological or physiological functions. Further, reports on the immunomodulatory effects of CSCEXs are summarized, and exosome engineering for CSC-targeting is also discussed.


2019 ◽  
Vol 14 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Gabriele D. Bigoni-Ordóñez ◽  
Daniel Czarnowski ◽  
Tyler Parsons ◽  
Gerard J. Madlambayan ◽  
Luis G. Villa-Diaz

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.


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